Bacillus subtilis a gram-positive soil bacterium, like all living cells, encounters stress in its natural habitat. Environmental stress activates a collection of more than 200 genes which make up the B. subtilis general stress regulon. The general stress regulon is controlled by sigma-B, a transcription factor activated by either physical stress or nutritional stress. The activity state of sigma-B is controlled by an anti-sigma-B protein and its antagonist, these in turn, are regulated by stress-responsive kinase/phosphatase cascades. Although the biochemical processes leading to sigma-B activation have been characterized in some detail, the mechanism by which stress is perceived by these regulators is unknown. The objective of this proposal is to identify genes whose products are needed to trigger the physical stress pathway of sigma-B activation. It is anticipated that the identity of such genes will offer clues into the processes by which stress is communicated to the sigma-B regulators.